Impedance measurements of bodily matter

ABSTRACT

A method and apparatus for generating an impedance spectrum which is characteristic of a sample of bodily matter in a resonant circuit and which may be used to analyse the sample.

BACKGROUND OF THE INVENTION

1. Field of Invention

The present invention relates to a method and apparatus for generatingan impedance spectrum which is characteristic of a sample of bodilymatter in a resonant circuit.

2. Related Art

Numerous conditions may give rise to abnormalities in bodily tissue (egdisease, wounding, infection or cancer). In many cases, diagnosis mayonly be possible by taking a biopsy for ex vivo analysis. As well asbeing invasive, this method is inefficient and unable to provide rapidonline data. In addition, the removal of a biopsy may cause significantdiscomfort to the subject

The electrical impedance spectrum exhibited by a sample or bodily matteris dependent upon its composition. Although bodily matter has previouslybeen analysed by multi-frequency ac impedance measurements, the circuitsused were not resonant. For example, it is known to use electricalimpedance measurements to determine the status of a part of the body(see inter alia Dijkstra et al, Clinical Applications of ElectricalImpedance Tomography, J Med. Eng. and Tech, 17, 3, 98—98).

SUMMARY OF THE INVENTION

The present invention is based on the recognition that the impedancespectrum of a sample of bodily matter which has been made part of aresonant electrical circuit is surprisingly sensitive to thecharacteristics of the sample of bodily matter and may be used toprovide reliable and accurate detection of abnormalities in the sample(eg damaged or infected tissue). Moreover, the present invention iscapable of providing information in real time whilst being substantiallynon-invasive.

Thus viewed from one aspect the present invention provides a method forgenerating an impedance spectrum which is characteristic of a sample ofhuman or non-human bodily matter (eg tissue), said method comprising thesteps of:

applying an electrical signal to the sample of bodily matter at each ofa plurality of frequencies in a frequency range including a resonantfrequency; and

measuring an impedance quantity at each of the plurality of frequenciesin the frequency range whereby to generate the impedance spectrum.

Whilst not wishing to be bound by any theoretical consideration, it isnonetheless noted that an impedance quantity (Z⁺) reflects the responseof a sample of bodily matter (eg tissue) to an alternating electricfield stimulus and may be considered as a type of transfer functionexpressing the ratio of the output voltage to input current. Thistransfer function is related to the composition of the sample of bodilymatter being tested

The impedance quantity may be considered equivalent to resistance (R)which is measured using direct current. However, in the frequency domainit is a complex number having both a real and an imaginary componentexpressed by:

Z ⁺ =R+jX

(where X is the reactance which is a function of frequency and j=−1).The resonant frequency is that frequency at which reactance is zero andmay be regarded as the frequency at which the inductive and capacitivecontributions to the reactance cancel out.

Impedance quantities which may be measured in accordance with theinvention include the reactance (X) and the phase angle (θ) which are bydefinition zero at the resonant frequency. A preferred impedancequantity is the dissipation factor (DF) defined as:

DF=R/X

DF is a measure of the energy dissipated in a circuit by the resistiveheating relative to the energy stored in a circuit by capacitive andinductive mechanisms. DF reaches a maximum as X reaches zero (ie as theresonant frequency is reached)

In one embodiment of the invention, the electrical signal is a timevarying electrical signal. Preferably, the time varying electricalsignal is an alternating current (ac) signal.

The measurement of the impedance quantity may comprise a time tofrequency domain transformation of the time varying electrical signal.The steps involved in such a measurement will be generally familiar tothose skilled in the art (see for example Perturbation Signals forSystem Identification, ed K Godfrey, Prentice Hill, 1993, UK). The timevarying electrical signal may be periodic and may comprise any suitablefunction or code eg a pseudo random binary sequence (PRBS), a Golaycode, a Walsh function, a Huffman sequence or any other suitable codedsequence. Other suitable signals, codes or methodologies such as whiteGaussian noise or wavelet analysis may be employed and will be generallyfamiliar to those skilled in the art (see for example Signal ProcessingMethods for Audio Images and Telecommunications, ed P M Clarkson and HStork, Academic Press, London, 1995).

The electrical signal may be applied by at least two electrodes. Theelectrodes may be in direct or indirect electrical contact With thesample of bodily matter. For example, an insulating layer may be placedover one or more of the electrodes so that the electrodes are inindirect electrical contact with the sample of bodily matter.

In a preferred embodiment of the method of the invention, the electricalsignal may be applied by one or more microelectrodes of the typegenerally or specifically disclosed in WO-A-99/60392 (Farfield SensorsLimited) or specifically claimed therein.

Alternatively, the electrical signal may be applied via at least twowindings. The windings may be in direct or indirect electrical contactwith the sample of bodily matter.

A means for varying the frequency of the applied electrical signal maybe used to apply the electrical signal at a plurality of frequencies ina range including the resonant frequency. For example, at least oneinductor or one or more quartz crystal resonators may be used.Conveniently, the means for varying the frequency of the appliedelectrical signal ensures that the resonant frequency is below about 1MHz. At such a resonant frequency, problems associated withinstrumentation and digitisation are generally reduced.

In a preferred embodiment, the method of the invention comprises thestep of comparing the impedance spectrum of an abnormal sample of bodilymatter with the impedance spectrum of a normal (ie healthy) sample ofbodily matter to deduce the relative characteristics of the normal andthe abnormal sample. The term “abnormal sample of bodily matter” mayinclude inter alia cancerous, scarred, infected or diseased tissue.

For example, the impedance spectra may be compared to deduce a shift inthe resonant frequency or a difference in the magnitude of the impedancequantity at or near to the resonant frequency. In turn, the relativecharacteristics of the abnormal and normal sample of tissue may bededuced in a further step.

The method of the invention may be used to detect abnormalities innormal bodily tissue. For example, the method may be advantageously usedto detect abnormalities in external bodily tissue including inter aliaskin abnormalities, tooth decay, gum disease or cancerous growths.However the method may equally be used on interior bodily tissue todetect abnormalities such as bone abnormalities or cancerous tissue.

In a preferred embodiment, the method of the invention comprises thefollowing steps:

applying a first electrical signal to a first sample of bodily matter ateach of a plurality of frequencies in a first frequency range includinga resonant frequency;

measuring an impedance quantity at each of the plurality of frequenciesin the first frequency range whereby to generate an impedance spectrumof the first sample;

applying a second electrical signal to a second sample of bodily matterat each of a plurality of frequencies in a second frequency rangeincluding a resonant frequency;

measuring an impedance quantity at each of the plurality of frequenciesin the second frequency range whereby to generate an impedance spectrumof the second sample;

comparing the impedance spectrum of the first sample and the impedancespectrum of the second sample; and

deducing the relative characteristics of the first and the second sampleof bodily matter.

By way of example, the first sample may be a normal sample of bodilymatter (eg healthy tissue) and the second sample may be an abnormalsample of bodily matter. The step of comparing may comprise calculatingthe shift in resonant frequency between the normal sample of bodilymatter and the abnormal sample of bodily matter.

The sensitivity of the method of the invention is such that the shift inthe resonant frequency between a sample of normal and a sample ofabnormal bodily matter may be significant and may be a downward or anupward shift. For example, a downward shift in resonant frequency istypically characteristic of a sample of diseased skin vis a vis a sampleof normal skin whilst an upward shift in resonant frequency is typicallycharacteristic of a sample of scar tissue vis a vis a sample of normalskin. Typically the shifts are as significant as −90 kHz and +100 kHzrespectively.

Alternatively, the step of comparing may comprise calculating a changein the magnitude of the impedance quantity at the resonant frequency.This is useful where the impedance quantity is the dissipation factor.

Viewed from a further aspect the present invention provides an apparatusfor generating an impedance spectrum which is characteristic of a sampleof human or non-human bodily matter (eg tissue), said apparatuscomprising:

electrical signal applying means adapted to apply a time varyingelectrical signal to the sample of bodily matter at each of a pluralityof frequencies in a frequency range including a resonant frequency; and

measuring means for measuring an impedance quantity characteristic ofthe sample of bodily matter at each of the plurality of frequencies inthe frequency range whereby to generate the impedance spectrum.

In an embodiment of the apparatus of the invention, the electricalsignal applying means is capable of applying an ac signal of variablefrequency.

In an embodiment of the apparatus of the invention, the electricalsignal applying means is capable of applying a time varying electricalsignal which is periodic.

The electrical signal applying means may be adapted for use ex vivo orin vivo (externally or internally) as required. The electrical signalapplying means may be capable of being positioned in direct or indirectelectrical contact with the bodily matter.

The electrical signal applying means may comprise a means for varyingtie frequency of the electrical signal to apply the electrical signal ata plurality of frequencies in a range including the resonant frequency.For example, the apparatus may further comprise at least one inductor orat least one quartz crystal resonator. Conveniently, the means forvarying the frequency of the electrical signal is arranged so that theresonant frequency is below about 1 MHz. At such a resonant frequency,problems associated with instrumentation and digitisation are generallyreduced.

The electrical signal applying means may comprise at least twoelectrodes. The electrodes may be capable of being positioned in director indirect electrical contact with the bodily matter. For example, oneor more of the electrodes may comprise an outer insulating layer so thatthe electrodes are capable of being positioned in indirect electricalcontact with the sample of bodily matter.

Numerous electrode materials, sizes and configurations are suitable (asdesired) for the preferred embodiment. Generally, the configuration andmaterial may be tailored to the end use. For example, planar electrodesmay be used where the sample of bodily matter comprises the skin. Suchplanar electrodes may be rectangular or half ring configurations asdesired. Multiple electrode arrangements may be used where desired.Modulation of the applied electrical field strength is possible to findthe optimum working field strength or to provide additional informationon the tissue sample.

In a preferred embodiment of the apparatus of the invention, theelectrical signal applying means comprises one or more microelectrodesof the type generally or specifically disclosed in WO-A-99/60392(Farfield Sensors Limited) or specifically claimed therein.

The electrical signal applying means may comprise at least two windings.The windings may be capable of being positioned in direct or indirectelectrical contact with the bodily matter. For example, the windings maybe potted in a casing of an inert material. This embodiment acts in asimilar manner to a transformer ie wherein one winding is energised as aprimary winding and drives a second winding which acts as a secondarywinding. A current may be induced in the secondary winding with anefficiency which depends on the impedance of the medium between theprimary and secondary windings.

In an embodiment of the invention, the electrical signal applying meanscomprises a probe adapted to be inserted into a bodily cavity and toenable measurement of the impedance spectrum characteristic of thesurrounding tissue. The probe may be useful in internal use eg in thedetection of cancer (eg cervical cancer). The probe may comprise one ormore suitably shaped electrodes (eg needle electrodes) insertable intothe bodily cavity.

In an embodiment of the apparatus of the invention, the measuring meansmay comprise an impedance analyser.

In an embodiment of the apparatus of the invention, the measuring meansmay be capable of performing a time to frequency domain transformationof the time varying electrical signal.

Viewed from a yet further aspect the present invention provides the useof an apparatus as hereinbefore defined for generating an impedancespectrum at each of a plurality of frequencies in a frequency rangeincluding a resonant frequency which is characteristic of a sample ofhuman or non-human bodily matter. Preferably the sample is an exteriorpart of the human or non-human body (eg the skin).

Viewed from a yet still further aspect the present invention provides akit of parts suitable for generating an impedance spectrum at each of aplurality of frequencies in a frequency range including a resonantfrequency which is characteristic of a sample of human or non-humanbodily matter, said kit comprising:

at least two electrodes for applying alternating current to the sampleof bodily matter;

an inductor; and

an impedance analyser capable of measuring an impedance quantity at eachof the plurality of frequencies in the frequency range including theresonant frequency whereby to generate the impedance spectrum.

BRIEF DESCRIPTION OF THE DRAWINGS

Methods and apparatus in accordance with the invention will now bedescribed in a non-limitative sense with reference to the accompanyingFigures in which;

FIG. 1 is a schematic illustration of a first embodiment of an apparatusof the invention;

FIG. 2 illustrates dissipation factor as a function of frequency forsamples of undamaged skin and scar tissue; and

FIG. 3 illustrates dissipation factor as a function of frequency forsamples of non-infected and infected skin.

DETAILED DESCRIPTION

In a first embodiment of the apparatus of the invention shownschematically in FIG. 1 and designated generally by reference numeral 1,a time varying electrical signal was applied to a sample of bodilymatter 10 by two nickel coated steel electrodes 11 and 12 in directcontact therewith. In the first example, the sample of bodily matter wastissue on the back of a human subject's hand which exhibited a small dryscar whose surrounding area was slightly reddened. An inductor 15 wasprovided in series with electrodes 11 and 12 to ensure that the circuitwas capable of resonating. The value of the inductor 15 used (324 mH)was such that the resonant frequency occurred within a tractable rangeie at around 1 MHz or less. The applied voltage was 0.2 volts peak topeak which caused minimal discomfort to the subject.

An ac signal of variable frequency was applied and the dissipationfactor was measured as a function of the frequency of the applied signalover a frequency range which includes a resonant frequency. Thedissipation factor was measured by an impedance analyser 13 (HewlettPackard 4192A). Data were transferred to a personal computer 14 forfurther analysis.

The electrodes 11 and 12 were placed approximately 5 mm from the scartissue and the dissipation factor spectrum characteristic of the normalsample of tissue was measured at 10 kHz intervals in the range 1 to 800kHz. This measurement was repeated and the results are shown in FIG. 2(reference 21). The electrodes 11 and 12 were then placed onto the scarand a similar reading (reference 22) was obtained for the abnormal(scar) tissue also shown in FIG. 2.

It will be seen that the scar tissue and the normal tissue exhibit asignificantly different impedance spectrum. The resonant frequencyobserved for scar tissue is about 100 kHz higher than the resonantfrequency of normal tissue. It will also be noted that the upward shiftin resonant frequency is accompanied by an apparent increase in thevalue of the dissipation factor. The maximum calculated value of thedissipation factor is critically dependent upon the value of thereactance as it approaches zero. The calculated value of the maximumdissipation factor is therefore dependent upon the frequency step sizeand its proximity to the true resonant frequency. The latter is likelyto be temperature dependent although given time for any subject toacclimatise to the environment in which the measurements are conductedthis may be controlled. Notwithstanding these comments, it is believedthat the magnitude of the dissipation factor will provide usefulinformation additional to that provided by the resonant frequency.

FIG. 3 illustrates the dissipation factor as a function of frequency fora normal and an abnormal sample of skin tissue from the palm of asubject who has an area of diseased skin (dermatitis). Impedancemeasurements over the range 1-870 kHz were conducted. The normal sampleexhibited a resonant frequency at about 460 kHz while the abnormal(diseased) sample was considerably lower at about 370 kHz (references 31and 32 respectively) It will be noted that the downward shift inresonant frequency characteristic of diseased skin is opposite to theupward shift in resonant frequency characteristic of scar tissue. Thisleads to the possibility of distinguishing two skin conditions.

What is claimed is:
 1. A method for generating an impedance spectrumwhich is characteristic of a sample of human or non-human bodily matter,said method comprising the steps of: applying a first electrical signalto a first sample of bodily matter at each of a plurality of frequenciesin a first frequency range including a resonant frequency; measuring animpedance quantity at each of the plurality of frequencies in the firstfrequency range whereby to generate an impedance spectrum of the firstsample; applying a second electrical signal to a second sample of bodilymatter at each of a plurality of frequencies in a second frequency rangeincluding a resonant frequency; measuring an impedance quantity at eachof the plurality of frequencies in the second frequency range whereby togenerate an impedance spectrum of the second sample; comparing theimpedance spectrum of the first sample and the impedance spectrum of thesecond sample; and deducing the relative characteristics of the firstand second sample of bodily matter.
 2. A method as claimed in claim 1wherein said bodily matter is bodily tissue.
 3. A method as claimed inclaim 1 wherein said impedance quantity is the dissipation factor.
 4. Amethod as claimed in claim 1 wherein said electrical signal is a timevarying electrical signal.
 5. A method as claimed in claim 4 wherein thetime varying electrical signal is periodic.
 6. A method as claimed inclaim 4 wherein said time varying electrical signal is an alternatingcurrent signal.
 7. A method as claimed in claim 4, wherein themeasurement of the impedance quantity is a time to frequency domaintransformation of the time varying electrical signal.
 8. A method asclaimed in claim 7 wherein the impedance spectra may be compared todeduce a shift in the resonant frequency or a difference in themagnitude of the impedance quantity at or near to the resonantfrequency.
 9. A method as claimed in claimed 1 wherein the first sampleis a normal sample of bodily matter and the second sample is an abnormalsample of bodily matter.
 10. A method as claimed in claim 1 wherein thecomparing step comprises: calculating a shift in resonant frequencybetween the normal sample of bodily matter and the abnormal sample ofbodily matter.
 11. A method as claimed in claim 10 wherein the shift inresonant frequency is a downward shift in resonant frequency.
 12. Amethod as claimed in claim 10 wherein the shift in resonant frequency isan upward shift in resonant frequency.
 13. A method as claimed in claim10 wherein the shift in resonant frequency is in the range −90 kHz to+100 kHz.
 14. A method as claimed in claim 1 wherein the comparing stepcomprises: calculating a change in magnitude of the impedance quantityat or near to the resonant frequency.
 15. A method as claimed in claim 1conducted in vivo wherein the sample of bodily matter is exterior orinterior body tissue.
 16. A method as claimed in claim 1 wherein thesample of bodily matter is selected from the group consisting ofcancerous, scarred, infected or diseased tissue.
 17. An apparatus forgenerating an impedance spectrum which is characteristic of a sample ofhuman or non-human bodily matter, said apparatus comprising: electricalsignal applying means adapted to apply a time varying electrical signalto the sample of bodily matter at each of a plurality of frequencies ina frequency range including a resonant frequency, wherein the electricalsignal applying means includes a means for varying the frequency of theelectrical signal to apply the electrical signal at a plurality offrequencies in a range including the resonant frequency; and measuringmeans for measuring an impedance quantity characteristic of the sampleof bodily matter at each of the plurality of frequencies in thefrequency range whereby to generate the impedance spectrum, wherein themeans for varying the frequency of the electrical signal comprises atleast one inductor or at least one quartz crystal resonator.
 18. Anapparatus as claimed in claim 17 wherein the electrical signal applyingmeans is capable of applying a time varying electrical signal which isperiodic.
 19. An apparatus as claimed in claim 17 wherein the electricalsignal applying means is adapted for use ex vivo or in vivo (externallyor internally).
 20. An apparatus as claimed in claim 17 wherein theelectrical signal applying means is capable of being positioned indirect or indirect electrical contact with the bodily matter.
 21. Anapparatus as claimed in claim 17 wherein the means for varying thefrequency of the electrical signal is arranged so that the resonantfrequency is below about 1 MHz.
 22. An apparatus as claimed in claim 17wherein the electrical signal applying means comprises at least twoelectrodes capable of being positioned in direct or indirect electricalcontact with the bodily matter.
 23. An apparatus as claimed in claim 17wherein the electrical signal applying means comprises at least twowindings capable of being positioned in direct or indirect electricalcontact with the bodily matter.
 24. An apparatus as claimed in claim 17wherein the electrical signal applying means comprises a probe adaptedto be inserted into a bodily cavity and to enable measurement of theimpedance spectrum characteristic of the surrounding tissue.
 25. Anapparatus as claimed in claim 17 wherein the measuring means comprisesan impedance analyzer.
 26. An apparatus as claimed in claim 17 whereinthe measuring means is capable of performing a time to frequency domaintransformation of the time varying electrical signal.
 27. A method forgenerating an impedance spectrum which is characteristic of a sample ofhuman or non-human bodily matter, said method comprising the steps of:applying an electrical signal to the sample of bodily matter at each ofa plurality of frequencies in a frequency range including a resonantfrequency; and measuring an impedance quantity at each of the pluralityof frequencies in the frequency range whereby to generate the impedancespectrum, wherein said impedance quantity is the dissipation factor. 28.A method for generating an impedance spectrum which is characteristic ofa sample of human or non-human bodily matter, said method comprising thesteps of: applying an electrical signal to the sample of bodily matterat each of a plurality of frequencies in a frequency range including aresonant frequency; and measuring an impedance quantity at each of theplurality of frequencies in the frequency range whereby to generate theimpedance spectrum, wherein the measurement of the impedance quantity isa time to frequency domain transformation of the time varying electricalsignal.